In an effort to determine if there are intrinsic morphological differences in the brains of patients with severe, unremitting psychosis and if such differences are related to a particular transmitter system, this section of the program has two objectives. First, we will attempt to replicate various morphometric findings in prefrontal, anterior cingulate, and entorhinal cortex, as well as the hippocampus of schizophrenics that have been reported by this laboratory and those of others. Second, in situ localization of GABA and glutamate high affinity binding in the same brain regions will be undertaken in an effort to test two hypotheses generated in the laboratory. Based on our previous investigations, we have postulated GABAnergic interneurons may be preferentially decreased, while glutamatergic associative fibers may be increased in some brain regions in this disorder. We hope to gain some understanding of whether central inhibitory and/or excitatory mechanisms may be altered by determining whether up- and down-regulation of the GABA and glutamate receptors, respectively, may occur in central corticolimbic regions of schizophrenic brain.